Facilitated Transport of Hydrophilic Salts by Mixtures of Anion and

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10142

J. Am. Chem. Soc. 1999, 121, 10142-10151

Facilitated Transport of Hydrophilic Salts by Mixtures of Anion and Cation Carriers and by Ditopic Carriers Lysander A. J. Chrisstoffels,† Feike de Jong,*,† David N. Reinhoudt,*,† Stefano Sivelli,‡ Licia Gazzola,‡ Alessandro Casnati,‡ and Rocco Ungaro‡ Contribution from the Department of Supramolecular Chemistry and Technology, MESA+ Research Institute, UniVersity of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands, and Dipartimento di Chimica Organica e Industriale, UniVersita` degli Studi, Vialle delle Scienze 78, 1-43100 Parma, Italy ReceiVed May 12, 1999

Abstract: Anion transfer to the membrane phase affects the extraction efficiency of salt transport by cation carriers 1 and 3. Addition of anion receptors 5 or 6 to cation carriers 1, 3, or 4 in the membrane phase enhances the transport of salts under conditions in which the cation carriers alone do not transport salt. The extraction of salt by the carrier mixtures is larger than by cation or anion carrier only, but the rate of diffusion is lower. Ditopic receptors 8 and 9 transport CsCl or KCl much faster than monotopic anion receptor 7 or cation receptors 1 and 2. The faster transport is due to a higher extraction constant Kex despite a lower diffusion constant of the ditopic salt complex.

Introduction Facilitated salt transport by neutral cation carriers is greatly affected by the hydrophobicity of the cotransported anion.1 The distribution of salt between an organic and aqueous phase is inversely related to the dehydration energy2 or the lyotropic number of the anion.3 In practice, only salts with lipophilic anions, such as NO3-, I-, or ClO4-, are transported in cationfacilitated transport.4 Transport of hydrophilic salts requires increased complex stability of the cation complex. However, we have previously shown that this leads to a higher kinetic stability of the complexes.5 Consequently, the rate-limiting step in the transport is no longer the rate of diffusion but the rate of decomplexation. This reduces both the rate of transport and the selectivity. In the literature, several systems have been reported that circumvent anion transfer in membrane transport. In the case of charged lipophilic carriers, a cation is transported in the opposite direction.6 Proton-ionizable macrocyclic carriers such * To whom the correspondence should be addressed. Fax: Int. code + (53)4894645. E-mail: [email protected]. † University of Twente. ‡ Universita ` degli Studi. (1) (a) Lamb, J. D.; Chrisstensen, J. J.; Izatt, S. R.; Bedke, K.; Astin, M. S.; Izatt, R. M. J. Am. Chem. Soc. 1980, 102, 3399. (b) Yoshida, S.; Hayano, S. J. Membr. Sci. 1982, 11, 157. (2) Olsher, U.; Hankins, M.; Kim, Y. D.; Bartsch, R. A. J. Am. Chem. Soc. 1993, 115, 3370. (3) Sakim, M.; Hayashita, T.; Yamabe, T.; Igawa, M. Bull. Chem. Soc. Jpn. 1987, 60, 1289. (4) For comprehensive reviews on cation-facilitated transport see: (a) Bartsch, R. A., Way, J. D., Eds.; Chemical Separations with Liquid Membranes; ACS Symposium Series Number 642; American Chemical Society: Washington, D.C., 1996. (b) de Jong, F.; Visser, H. C. In ComprehensiVe Supramolecular Chemistry; Atwood, J. L., Davies, J. E. D., MacNicol, D. D., Vo¨gtle, F., Lehn, J.-M., Reinhoudt, D. N., Eds.; Elsevier Science: Oxford, U.K., 1996; Vol. 10, Chapter 2. (5) Reichwein-Buitenhuis, E. G.; Visser, H. C.; de Jong, F.; Reinhoudt, D. N. J. Am. Chem. Soc. 1995, 117, 3913. (6) Fyles, T. M. In Inclusion Aspects of Membrane Chemistry; Osa, T., Atwood, J. L., Eds.; Kluwer Academic Publishers: Dordrecht, The Netherlands, 1991.

as crown ethers with pendant carboxylic acid or ammonium groups,7,8 diaza- and tetraazamacrocycles,9,10 and oxime carriers11 allow counter transport of protons. Also mixtures of neutral cation carriers and lipophilic anions have been used.12 Redoxdriven transport of cations is possible by cotransport of electrons with nickel bis(dithiolene) or anthraquinone.13 These systems form a lipophilic anion by reversible reduction and oxidation of the carrier. We study the transport of hydrophilic salts by mixtures of anion14 and cation15 receptors. The obvious extension of this work is to combine the anion and cation recognition site in a neutral ditopic or bifunctional (7) (a) Strzelbicki, J.; Bartsch, R. A. J. Membr. Sci. 1982, 10, 35. (b) Shinkai, S.; Kinda, H.; Araragi, Y.; Manabe, O. Bull. Chem. Soc. Jpn. 1983, 56, 559. (c) Fyles, T. M. J. Chem. Soc., Faraday Trans. 1 1986, 82, 617. (d) Walkowiak, W.; Brown, P. R.; Shukla, J. P.; Bartsch, R. A. J. Membr. Sci. 1987, 32, 59. (e) Brown, P. R.; Hallman, J. L.; Whaley, L. W.; Desai, D.; Pugia, M. J.; Bartsch, R. A. J. Membr. Sci. 1991, 56, 195. (8) Nakatsuji, Y.; Kobayashi, H.; Okahara, M. J. Org. Chem. 1986, 51, 3789. (9) (a) Nijenhuis, W. F.; Walhof, J. J. B.; Sudho¨lter, E. J. R.; Reinhoudt, D. N. Recl. TraV. Chim. Pays-Bas 1991, 110, 265. (b) Nakatsuji, Y.; Shimizu, H.; Morita, H.; Masuyama, A.; Okahara, M. Chem. Lett. 1992, 2185. (10) (a) Kimura, E.; Dalimunte, C. A.; Yamashita, A.; Machida, R. J. Chem. Soc., Chem. Commun. 1985, 1041. (b) Di Casa, M.; Fabbrizzi, L.; Perotti, A.; Poggi, A.; Tundo, P. Inorg. Chem. 1985, 24, 1610. (11) (a) Baker, R. W.; Tuttle, M. E.; Kelly, D. J.; Lonsdale, H. K. J. Membr. Sci. 1977, 2, 213. (b) Teramoto, M.; Tanimoto, H. Sep. Sci. Technol. 1983, 18, 871. (12) Ramadan, A.; Danesi, P. R. SolVent Extr. Ion. Exch. 1988, 6, 157. Parthasarthy, N.; Buffle, J. Anal. Chim. Acta 1991, 254, 9. Dadfarnia, S.; Shamsipur, M. J. Membr. Sci. 1992, 75, 61. Parham, H.; Shamsipur, M. J. Membr. Sci. 1994, 95, 21. (13) (a) Grimaldi, J. J.; Lehn, J.-M. J. Am. Chem. Soc. 1979, 101, 1333. (b) Chen, Z.; Gokel, G. W.; Echegoyen, L. J. Org. Chem. 1991, 56, 3369. (14) For a review on anion recognition: (a) Schmidtchen, F. P.; Berger, M. Chem. ReV. 1997, 97, 1609. (b) Bianchi, A., Bowman-James, K., Garcı´aEspan˜a, E., Eds. Supramolecular Chemistry of Anions; Whiley-VCH: New York, 1997. (c) Beer, B. D. Acc. Chem. Res. 1998, 31, 71. (d) Antonisse, M. M. G.; Reinhoudt, D. N. Chem. Commun. 1998, 443. (15) For a review on cation recognition: (a) Dietrich, B., Viout, P., Lehn, J.-M., Eds. Macrocyclic Chemistry; Verlagsgesellschaft mbH VCH: Weinheim, Germany, 1993. (b) Izatt, R. M.; Pawlak, K.; Bradshaw, J. S.; Bruening, R. L. Chem. ReV. 1995, 95, 2529.

10.1021/ja991588g CCC: $18.00 © 1999 American Chemical Society Published on Web 11/03/1999

Facilitated Transport of Hydrophilic Salts receptor.16 Our group and others have reported the complexation of salts in organic media by bifunctional receptors.16,17 In this paper, we describe the transport of hydrophilic salts when both the anion and cation are complexed either by two separate carriers or by one bifunctional receptor. First, the effect of anion transfer on cation-facilitated transport of potassium salts by carrier 1 and sodium salts by carrier 3 is described. In the second part salt transport by mixtures of cation carriers 1, 3, or 4 and anion carriers 5 or 6 is reported. Carriers 5 and 6 are uranyl salene receptors in which Lewis and Brønsted acidic sites are combined.18 We have successfully applied these as neutral anion carriers for the transport of lipophilic Cl- and H2PO4- salts.19 The mechanism of salt transport by the carrier mixtures has been compared with cation-facilitated transport of salt. Finally, the transport of CsCl and KCl by ditopic carriers 8 and 9 is described. Results and Discussion20 Synthesis of Anion Receptors, Cation Receptors, and Bifunctional Receptors. From the literature, it is known that (thio)ureas complex halides.21 Our group has reported the complexation of halides by (thio)urea functionalized calix[4]arenes.21d We have also demonstrated that K+ or Cs+ can be bound by calix[4]crown-522 and calix[4]crown-623 receptors, respectively. Combination of these binding sites on a calix[4]arene platform in the 1,3-alternate conformation (receptors 8 and 9) results in a bifunctional salt receptor. (16) For recognition of salts by bifunctional receptors see: (a) Olsher, U.; Frolow, F.; Dalley, N. K.; Weiming, J.; Yu, Z.-Y.; Knobeloch, J. M.; Bartsch, R. A. J. Am. Chem. Soc. 1991, 113, 6570. (b) Reetz, M. T.; Niemeyer, C. M.; Harms, K. Angew. Chem., Int. Ed. Engl. 1991, 30, 1472 (c) Arafa, E. A.; Kinnear, K. I.; Lockhart, J. C. J. Chem. Soc., Chem. Commun. 1992, 61. (d) Savage, P. B.; Holmgren, S. K.; Gellman, S. H. J. Am. Chem. Soc. 1993, 115, 7900. (e) Kinnear, K. I.; Mousley, D. P.; Arafa, E.; Lockhart, J. C. J. Chem. Soc., Dalton Trans. 1994, 3637. (f) Reetz, M. T.; Johnson, B. M.; Harms, K. Tetrahedron Lett. 1994, 35, 2525. (g) Savage, P. B.; Holmgren, S. K.; Gellman, S. H. J. Am. Chem. Soc. 1994, 116, 4069. (h) Rudkevich, D. M.; Brzozka, Z.; Palys, M.; Visser, H. C.; Verboom, W. Reinhoudt, D. N. Angew. Chem., Int. Ed. Engl. 1994, 33, 467. (i) Beer, P. D.; Drew, M. G. B.; Knubley, R. J.; Ogden, M. I. J. Chem. Soc., Dalton Trans. 1995, 3117. (j) Scheerder, J.; van Duynhoven, J. P. M.; Engbersen, J. F. J.; Reinhoudt, D. N. Angew. Chem., Int. Ed. Engl. 1996, 35, 1090. (17) Rudkevich, D. M.; Mercer-Chalmers, J. D.; Verboom, W.; Ungaro, R.; de Jong, F.; Reinhoudt, D. N. J. Am. Chem. Soc. 1995, 117, 6124. (18) (a) Rudkevich, D. M.; Stauthamer, W. P. R. V.; Verboom, W.; Engbersen, J. F. J.; Harkema, S.; Reinhoudt, D. N. J. Am. Chem. Soc. 1992, 114, 9671. (b) Rudkevich, D. M.; Verboom, W.; Brzozka, Z.; Palys, M.; Stauthamer, W. P. R. V.; van Hummel, G. J.; Franken, S. M.; Harkema, S.; Engbersen, J. F. J.; Reinhoudt, D. N. J. Am. Chem. Soc. 1994, 116, 4341. (c) Antonisse, M. M. G.; Snellink-Rue¨l, B. H. M.; Yigit, I.; Engbersen, J. F. J.; Reinhoudt, D. N. J. Org. Chem. 1997, 62, 9034. (19) Chrisstoffels, L. A. J., Ph.D. Thesis, University of Twente, Enschede, The Netherlands, 1998. (20) Preliminary results were described in: Visser, H. C.; Rudkevich, D. M.; Verboom, W.; de Jong, F.; Reinhoudt, D. N. J. Am. Chem. Soc. 1994, 116, 11554 and ref 17. (21) For complexation studies by (thio)urea based receptors see: (a) Adrian J. C., Jr.; Wilcox, C. S. J. Am. Chem. Soc. 1992, 114, 1398. (b) Kelly, T. R.; Kim, M. H. J. Am. Chem. Soc. 1994, 116, 7072. (c) Fan, E.; Arman, S. A. V.; Kincaid, S.; Hamilton, A. D. J. Am. Chem. Soc. 1993, 115, 369. (d) Scheerder, J.; Fochi, M.; Engbersen, J. F. J.; Reinhoudt, D. N. J. Org. Chem. 1994, 59, 7815. (e) Raposo, C.; Almaraz, M.; Martin, M.; Weinrich, V.; Mussons, L.; Alcazar, V.; Caballero, C.; Mosan, J. R. Chem. Lett. 1995, 759. (f) Wilcox, C. S.; Kim, E.-I.; Romano, S.; Kuo, L. H.; Burt, A. L.; Curran, D. P. Tetrahedron 1995, 51, 621. (g) Bu¨hlmann, P.; Nishizawa, S.; Xiao, K. P.; Umezawa, Y. Tetrahedron 1997, 53, 1647. (h) Jagessar, R. C.; Burns, D. H. Chem. Commun. 1997, 1685. (22) Casnati, A.; Pochini, A.; Ungaro, R.; Bocchi, C.; Ugozzoli, F.; Egberink, R. J. M.; Struijk, W.; Lugtenberg, R. J. W.; de Jong, F.; Reinhoudt, D. N. Chem. Eur. J. 1996, 2, 436. (23) Casnati, A.; Pochini, A.; Ungaro, R.; Ugozzoli, F.; Arnaud, F.; Fanni, S.; Schwing, M.-J.; Egberink, R. J. M.; de Jong, F.; Reinhoudt, D. N. J. Am. Chem. Soc. 1995, 117, 2767.

J. Am. Chem. Soc., Vol. 121, No. 43, 1999 10143 Scheme 1

The synthesis of cation carriers 1,22 2,23 and 324 was carried out according to literature procedures. The 15-crown-5 derivative (4) was prepared by alkylation of 2-hydroxymethyl-15-crown-5 with 8(-bromooctyl)-2-nitrophenyl ether25 in the presence of 1.1 equiv of NaH in acetonitrile. The syntheses of lipophilic uranyl salene carriers 5 and 6 will be published elsewhere.19 The preparation of dipropoxy-bis(2-ethylhexylthioureidopropoxy) calix[4]arene receptor 7 is depicted in Scheme 1. First, calix[4]arene 10 was reacted with 3-bromopropyl phthalimide in the presence of 2.5 equiv of K2CO3 to give bis(3-phthalimidopropoxy)-calix[4]arene 11 in 80% yield. Subsequently, calix[4]arene 11 was reacted with propyl iodide using Cs2CO3 as a base to give dipropoxy-bis(3-phthalimidopropoxy) calix[4]arene 12 in 52% yield. The 1,3-alternate conformation of calix[4]arene 12 was confirmed by the carbon absorption of the bridging methylene groups (ArCH2Ar) of the calix[4]arene present at 37.3 ppm in the 13C NMR spectrum and the singlet around 3.68 ppm in the 1H NMR spectrum for the corresponding methylene hydrogens.26 The phthalimido groups were removed with hydrazine hydrate in EtOH to give bis(3-aminopropoxy)calix[4]arene 13 in 96% yield. Bis(2-ethylhexylthioureido)calix[4]arene receptor 7 was obtained by conversion of calix[4]arene 13 to the corresponding bis(isothiocyanatopropoxy) calix[4]arene 14 and subsequent reaction with 2-ethylhexylamine. The synthesis of bis(thioureido)calix[4]crown-5 8 and bis(thioureido)calix[4]crown-5 9 is depicted in Scheme 2. Calix[4]crown-5 15 and calix[4]crown-6 16, both having the 1,3alternate conformation, were synthesized by reacting calix[4]arene 11 with tetra- or pentaethylene glycol di-p-toluene sulfonate, respectively, and 2.5 equiv of Cs2CO3 as a base in refluxing MeCN. The 1,3-alternate conformation was confirmed by 13C NMR spectroscopy as the carbon absorption of the bridge CH2 of the calix[4]arene is present at 38 ppm.26 The phthalimido groups of 15 and 16 were removed with hydrazine monohydrate in refluxing ethanol to give the bis(3-aminopropoxy)calix[4]crown derivatives 17 and 18, respectively. For the synthesis of the ditopic receptors 8 and 9, first bis(3-aminopropoxy)calix[4]crown-5 17 and bis(3-aminopropoxy)calix[4]crown-6 18 were converted with thiophosgene in the presence of triethylamine in toluene to the corresponding bis(3-isothiocyanatopropoxy)calix[4]crown derivatives 19 and 20. Subsequently, these were (24) Nijenhuis, W. F.; Buitenhuis, E. G.; de Jong, F.; Sudho¨lter, E. J. R.; Reinhoudt, D. N. J. Am. Chem. Soc. 1991, 113, 7963. (25) Visser, H. C.; Vink, R.; Snellink-Rue¨l, B. H. M.; Kokhuis, S. B. M.; Harkema, S.; de Jong, F.; Reinhoudt, D. N. Recl. TraV. Chim. PaysBas 1995, 114, 285. (26) Molins, M. A.; Nieto, P. M.; Sa`nchez, C.; Prados, P.; de Mendoza, J.; Pons, M. O. J. Org. Chem. 1992, 57, 6942.

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Table 1. Transport Parameters Dm, Kex, and ∆Gex,NPOE for the Transport of KX Salts by Carrier 1 and of NaX Salts by Carrier 3; [1]m or [3]m ) 10 mM transport of KX by carrier 1

transport of NaX by carrier 3

anion X-

Dm (10-12 m2 s-1)

Kex (M-1)

∆Gex,NPOE(KX) (kJ mol-1)a

Dm (10-12 m2 s-1)

Kex (M-1)

∆Gex,NPOE(NaX) (kJ mol-1)a

∆Gtr,NPOE(X-) (kJ mol-1)b

ClO4SCNINO3BrCNCl-

7.7 10.8 8.2 8.8 8.4 10 10.4

3.7 × 104 1.3 × 103 9.0 × 102 1.8 × 102 3.4 2.8 × 10-1 3.5 × 10-2

-26.0 -17.8 -16.8 -12.9 -3.0 3.2 8.3

8.0 8.9 8.5

14 4.0 × 10-1 1.2 × 10-1

-6.5 2.3 5.3

10.6 19.2 21.1 21.8 33.8 37.1 43.1

a

∆Gex,NPOE(MX) calculated from Kex (M-1). b Taken from ref 19.

replaced by Cl-. The transport of KH2PO4 was too low for an accurate determination of Dm and Kex; hence Kex of 1‚KH2PO4 is much smaller than that of 1‚KCl. For carrier 3, accurate values of Dm and Kex were only obtained for NaClO4, NaI, and NaSCN. The corresponding Gibbs free energies of extraction (∆Gex,NPOE(MX)) were calculated from Kex according to eq 2 (Table 1).

Scheme 2

∆Gex,NPOE(MX) ) -RT ln(Kex) with Kex )

[ML+]m[X-]m [M+]s[L]m[X-]s

(2)

The cation complex and anion are solvent-separated ions in the membrane phase.19 In this case ∆Gex,NPOE(MX) is the sum of the Gibbs free energy of cation transfer ∆Gtr,NPOE(M+), the Gibbs free energy of anion transfer ∆Gtr,NPOE(X-), and the Gibbs free energy of cation complexation ∆Ga,NPOE(M+). reacted with 2-ethylhexylamine in chloroform to give the ditopic carriers 8 and 9.27 Effect of Cotransported Anions on Cation-Facilitated Transport. The transport of salts by potassium carrier 1 and sodium carrier 3 was measured as a function of the salt activity as to determine the extraction coefficient Kex (see eq 2) and diffusion constant Dm of the carrier complexes from eq 1 (Table 1). The model has recently been developed in our group24 and applied to describe the facilitated transport of alkali24 and earthalkaline22,23 metal salts and silver salts.28

J0 )

Dm [-Kexas2 + x(Kexas2)2 + 4L0Kexas2] 2dm

(1)

The diffusion coefficients are all in the same range; 8 × 10-12 to 11 × 10-12 m2 s-1.29 Apparently, the cotransported anion only slightly affects the rate of diffusion in the membrane phase.30,31 The extraction constant (Kex), however, is strongly anion-dependent; it decreases by a factor of 106 when ClO4- is (27) Lipophilic, branched alkyl chains were attached to provide sufficient lipophilicity and to increase the solubility of the carriers in organic solutions. (28) Struck, O.; Chrisstoffels, L. A. J.; Lugtenberg, R. J. W.; Verboom, W.; van Hummel, G. J.; Harkema, S.; Reinhoudt, D. N. J. Org. Chem. 1997, 62, 2487. (29) Dm is the membrane diffusion coefficient. Dm is affected by the membrane characteristics, tortuosity Θ, and porosity τ. A diffusion coefficient Db in the bulk solvent can be calculated from Dm according to Db ) (τ/Θ)Dm. (30) The diffusion coefficient DMX of an electrolyte MX in dilute solution can be calculated from the individual diffusion coefficients (DM and DX): DMX ) (2DMDX)/(DM + DX). As the diffusion coefficients of the cation DM and the anion DX are inversely related to the radius of the diffusing species, DX will be much larger than DM. (31) Cussler, E. L., Ed. Diffusion; Mass transfer in Fluid Systems, 2nd ed.; Cambridge University Press: Cambridge, U.K., 1997.

∆Gex,NPOE(MX) ) ∆Gtr,NPOE(M+) + ∆Gtr,NPOE(X-) + ∆Ga,NPOE(M+) (3) For carrier 1, ∆Gex,NPOE(KX) is indeed related linearly to the Gibbs free energies of anion transfer to NPOE (∆Gex,NPOE(X-))19 with the expected slope of 1 (y ) 1.072x - 37.9, R2 ) 0.990). A similar relation is observed for the transport of NaX by carrier 3 (y ) 1.093x - 18.2, R2 ) 0.994). Equation 3 illustrates the limitations of the application of neutral cation carriers. Salt transport is not efficient in practice when ∆Gex,NPOE(MX) is too large (>10 kJ mol-1). This situation occurs when the relative contribution of ∆Ga,NPOE(M+) is not sufficient to compensate for the unfavorable Gibbs free energy of salt transfer. In this case, both an anion receptor and a cation receptor should be used in the membrane. The complexation in the membrane solvent is described by eq 4.

[LM]m + [M+]m a [LMM+]m with Ka,M ) +

-

[LX]m + [X ]m a [LXX ]m with Ka,X )

[LMM+]m [LM]m[M+]m

[LXX-]m [LX]m[X-]m

(4)

When [LMM+]m . [M+]m and [LXX-]m . [X-]m, the cooperative extraction of salt Kcoop ex is defined by eq 5 and 6 in which Kp, Ka,X, and Ka,M are the equilibrium constants for salt partitioning, anion complexation, and cation complexation, coop respectively. ∆Gex,NPOE (MX) was derived from Kcoop (eq 7), ex from which it is clear that salt extraction can be enhanced, because of the additional term for anion complexation, ∆Ga,NPOE(X-).

Facilitated Transport of Hydrophilic Salts

J. Am. Chem. Soc., Vol. 121, No. 43, 1999 10145

Chart 1

Figure 1. Transport of NaCl by mixtures of carriers 3 and 5 and of KCl by mixtures of carriers 1 and 5; [3 + 5]m ) [1 + 5]m ) 15 mM, [NaCl]s ) 1.0 M (9) and [KCl]s ) 25 mM (b).

Figure 2. Transport of KCl by carrier mixtures of 4 and 5; [4 + 5]m ) 15 mM, [KCl]s ) 0.5 M (2), 1.0 M (9), and 1.5 M ([).

[LX]m + [LM]m + [M+]aq + [X-]aq a [LXX-]m + [LMM+]m (5) Kcoop ex

) KpKa,XKa,M )

[LXX-]m[LMM+]m [LX]m[LM]m[M+]aq[X-]aq

(6)

coop ∆Gex,NPOE (MX) ) ∆Gtr,NPOE(X-) + ∆Gtr,NPOE(M+) +

∆Ga,NPOE(M+) + ∆Ga,NPOE(X-) (7) Cooperative Salt Transport with Carrier Mixtures. Transport of KCl, NaCl, and KH2PO4 with mixtures of cation carriers 1, 3, and 4 and anion carriers 5 and 6 (Chart 1) was measured as a function of the ratio of anion and cation carrier in the membrane phase keeping the total carrier concentration constant ([LX + LM]m ) 15 mM). First, KCl was transported from a low initial source phase concentration with mixtures of calix[4]crown-5 1 and uranyl salene 5. NaCl was transported from a high source phase concentration by mixtures of calix[4]arene tetraester 3 and uranyl salene 5 to promote salt extraction to the membrane phase (Figure 1). Neither the cation carrier nor anion carrier alone transports salt, but the carrier mixtures do. For the mixtures of carriers of both 1 and 5 and 3 and 5, the transport-rate reaches a maximum at equal concentration of anion carrier and cation carrier (Figure 1). The ratio of anion carrier vs cation carrier for which the flux is maximal is directly related to the stoichiometry of the carrier complexes in the membrane phase. A maximum flux at 1:1 ratio of anion carrier and cation carrier indicates that cooperative salt extraction occurs by complexes that have a 1:1 stoichiometry. We further studied the influence of complex stoichiometries on the transport of KCl with mixtures of 15-crown-5 derivative 4 and uranyl salene 5 (Figure 2). It is known from complexation studies and crystallography data that 15-crown-5 derivatives form 2:1 sandwich complexes with K+.32 Transport of KCl by (32) Cox, B. G., Schneider, H., Eds. Studies in Physical and Theoretical Chemistry; Elsevier Science: Amsterdam, The Netherlands, Vol. 76, 1992.

Figure 3. Transport of KH2PO4 by mixtures of carriers 1 and 5 ([), carriers 1 and 6 (9), and carriers 4 and 5 (b); [1 + 5]m ) [1 + 6]m ) [4 + 5]m ) 15 mM, [K2HPO4 + KH2PO4]s ) 0.05 M, pHs ) 6.7.

15-crown-5 4 or uranyl salene 5 individually is low, but for mixtures of carriers 4 and 5, transport does occur. A maximum transport rate is now observed for a 2:1 ratio of cation carrier vs anion carrier. We also found that mixtures of cation carrier 1 and anion carriers 5 and 6 cooperatively transport KH2PO4.33 Fluxes were measured at pH ) 6.7 with mixtures of carriers 1 and 5 and carriers 1 and 6 as a function of the carrier composition in the membrane phase (Figure 3). Salt is not transported by the cation carrier or the anion carrier alone. Only carrier mixtures transport KH2PO4 with a maximum transport rate at a ratio of anion versus cation carrier of 2:1. Apparently, uranyl salenes form 2:1 complexes with H2PO4- in the membrane phase. Complexation studies with uranyl salene receptors studied by 1H NMR (33) The experiments have been carried out from a source phase at pHs ) 6.7 at which both HPO42- and H2PO4- are present at equal concentration. The type of anion transported was determined by salt transport ([KH2PO4 + K2HPO4]s ) 0.045 M) from an acidic (pH ) 4.5; J0 ) 14 × 10-8 mol m-2 s-1), neutral (pH ) 7.1; J0 ) 9.5 × 10-8 mol m-2 s-1), and basic (pH ) 9.2; J0 ) 0.8 × 10-8 mol m-2 s-1) source phase with a mixture of calix[4]crown-5 1 and uranyl salene 6 ([1]m ) [6]m ) 0.01 M). At low pHs, phosphate (H2PO4-) transport occurs. Moreover, the ratio of K+ versus total phosphate (PO43-) in the receiving phase was determined after transport from a neutral source phase: (K+)/(PO43-) ) 1.07. This strongly indicates that almost exclusive KH2PO4 transport takes place.

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Table 2. Diffusion Coefficients Dm, Dlag, and R for the Transport of KI, KCl, and KH2PO4 by Mixtures of Carriers 1 and 5 carrier transported Dmb (10-12 mixture salta m2 s-1) 1d 1 + 5e 1 + 5f

KI KCl KH2PO4

7.6 5.0 3.7

Rb

tlag (s)

0 800 0 501 0.17 1484

Dlag (10-12 Dmc (10-12 m2 s-1) m2 s-1) 19 13 4.5

12 5.8 3

a [KX]s ) 0.4 M. b Determined from eq 8. c Determined from Dlag. [1]m ) 0.01 M. e [1]m ) [5]m ) 0.01 M. f [1]m ) 0.01 M and [5]m ) 0.02 M.

d

spectroscopy confirm the 2:1 stoichiometry with H2PO4- in organic media.34 When salene 5 is mixed with 15-crown-5 4, the flux reaches a maximum at 1:1 carrier ratio. Because both 15-crown-5 4 and salene 5 form a dimeric complex with K+ and with H2PO4-, respectively, the 1:1 carrier ratio indicates a 2:2 complex stoichiometry. The Mechanism of Facilitated Salt Transport. The ratelimiting step of transport was determined from a measurement of the transport rate as a function of the membrane thickness dm.5 When L0J0-1 is plotted as a function of dm, the slope of the fitted line gives the mean diffusion coefficient of the complex and the intercept is indicative for a chemical resistance (eq 8).

Figure 4. The initial flux J0 as a function of the salt concentration for the transport of KI by carrier 1 (0.01 M) ([), KCl by a mixture of carriers 1 (0.01 M) and 5 (0.01 M) (2), and KH2PO4 by a mixture of carriers 1 (0.01 M) and 5 (0.02 M) (9).

dm L0 ) (1 + R) J0 Dm

Table 4. Selective and Uphill Transport of KCl in the Presence of NaCl by Carrier 1 and by a Mixture of Carriers 1 and 5; [KCl]s ) 2.5 × 10-4 M and [NaCl]s ) 0.25 M

(8)

The transport of KI, KCl, and KH2PO4 by mixtures of carriers 1 and 5 was measured as a function of the membrane thickness from a source phase concentration of 0.4 M to ensure that all carrier at the source phase interface is present as complex.5 The mean diffusion coefficients Dm and R are given in Table 2. The intercept of the fitted lines is very small (R , 1). Thus the transport is diffusion-limited for all systems. With more than one carrier involved in transport, the apparent diffusion coefficient Dm decreases (Table 2) in agreement with the StokesEinstein equation. Lag-time experiments yield independent values for Dm.35 From the experimental lag time tlag, Dlag ) dm/6tlag was calculated (Table 2). The value for Dm was calculated from Dlag by Dm ) ΘDlag, Θ being the porosity of the membrane. The values for Dm obtained from lag times are in reasonable agreement with those obtained from flux measurements. The influence of the salt concentration on transport is shown in Figure 4. The transport rate increases with the salt concentration but reaches a maximum (J0,max), indicating that all carrier at the interface becomes complexed at high salt concentrations. Because the transport is diffusion-limited, Dm can be calculated from J0,max according to eq 9 (Table 3).24

J0,max )

D m L0 dm

(9)

The diffusion coefficients determined by different methods (Tables 2 and 3) are the same within experimental error and the relative order is Dm(1‚KCl) > Dm((1 + 5)‚KCl) > Dm((1 + 5)‚KH2PO4). The efficiency of selective uphill transport was determined for calix[4]crown-5 1 alone and for a mixture of calix[4]crown5 1 and uranyl salene 5 (1:1 stoichiometry). Experiments were (34) Antonisse, M. A. Ph.D. Thesis, University of Twente, Enschede, The Netherlands, 1998. (35) Bromberg L.; Levin, G.; Kedem, O. J. Membr. Sci. 1992, 72, 41.

Table 3. Maximum Flux J0,max and Diffusion Coefficient Dm for the Transport of KI, KCl and KH2PO4 by Mixtures of Carriers 1 and 5 carrier mixture

transported salt

J0,max (10-7 mol m-2 s-1)

Dma (10-12 m-2 s-1)

Dmb (10-12 m2 s-1)

1 1+5 1+5

KI KCl KH2PO4

8.1 5.7 3.0

8.1 5.7 3.0

7.7 5.7 3.4

a D value from J b m 0,max (Figure 4). Dm value from the transport as a function of the carrier concentration ([salt]s ) 0.4 M).

time (103 s)

carrier 1

67 67 137 137

0.01 0.01 0.01 0.01

a

S)

carrier 5 0.01 0.01

%Na+ transported

%K+ transported

selectivity Sa (103)

0.0018 0.0064 0.0020 0.0040

7.8 60.1 14.8 95

4.3 9.4 7.4 23.8

(%K+/%Na+).

performed with 2.5 × 10-4 M KCl/0.25 M NaCl as source phase (Table 4). With the carrier mixture, more than 50% of all K+ was transported in 1 day with a very high selectivity of about 104. After 2 days, more than 95% of all potassium was transported. The selective uptake of K+ by the calix[4]crown-5 in the membrane remains responsible for the high selectivities. Transport Efficiency by a Cation Carrier and by a Carrier Mixture. Although salt extraction into the membrane phase is clearly enhanced by addition of an anion carrier to a cation carrier, the mean diffusion coefficient of the carrier mixtures is lower than that of the cation carrier alone. These two counteracting factors may lead to a situation in which salt transport by carrier mixtures is not always most efficient. This is illustrated by the transport of KCl by calix[4]crown-5 1 alone in comparison with the transport by a (1:1) mixture of calix[4]crown-5 1 and uranyl salene 5 as a function of the source phase activity of KCl (Figure 5). At low salt activity, the extraction of salt by the mixture of 1 and 5 is higher; thus transport of KCl is most efficient. At high salt activity when the flux approaches a plateau, J0,max, salt transport by carrier 1 alone becomes more efficient due to a higher diffusion coefficient. The mean diffusion coefficient of 1‚KCl is 10.4 × 10-12 m2 s-1, whereas Dm ) 5.7 × 10-12 m2 s-1 for the transport of KCl by the mixture of 1 and 5. The limitations of carrier mixtures to transport salt are also reflected in the influence of the salt concentration on the facilitated transport of KCl by mixtures of calix[4]crown-5 1 and uranyl salene 5 at different carrier compositions (Figure 6).

Facilitated Transport of Hydrophilic Salts

J. Am. Chem. Soc., Vol. 121, No. 43, 1999 10147

Figure 5. The flux J0 as a function of the salt activity as for the transport of KCl by carrier 1 ([1]m ) 0.01 M, 9) and by the carrier mixture of 1 and 5 ([1]m ) [5]m ) 0.01 M, [).

Figure 6. Transport of KCl by carrier mixtures of 1 and 5; [1 + 5]m ) 15 mM, [KCl]s ) 0.05 ([), 0.25 (2), 0.5 (9), and 1.0 (b) M. Table 5. Transport Parameters Dm and Kex for the Transport of CsClO4 and CsCl by Calix[4]crown-6 Derivatives 2 and 9 carrier 2 2 9 9 a

transported salt MX CsClO4 CsCl CsClO4 CsCl

Dm (10-12 m2 s-1)

Kex (M-1)a

Gex,NPOE(MX) (kJ mol-1)

11 11 6.2 4.2

3130 0.0037 1970 472a

-19.9 13.9 -18.8 -15.2

K′ex (M-2) defined according to eq 12.

At low salt concentration ([KCl]s ) 0.025 M) the curve is a bell-shaped. With increasing salt concentration, facilitated transport of KCl by calix[4]crown-5 1 increases and exceeds the transport of KCl by the mixture of carriers 1 and 5. Ultimately, at high salt concentration substitution of part of calix[4]crown-5 1 by uranyl salene 5 results in less efficient transport!36 The observed trends can be rationalized by an extraction model based on salt partitioning and independent complexation of the anion and cation. (for further detail: see Supporting Information). Transport of CsCl with a Bifunctional Receptor. We have applied carriers 8 and 9 in SLMs to describe the mechanistic aspects of transport with bifunctional receptors.17 First, carriers 2 and 9 were used for the transport of CsCl and CsClO4.37 Since the transport of these salts is cation facilitated, eq 1 can be applied to describe the fluxes and determine values for Kex and Dm.24 The transport of CsClO4 by monotopic carrier 2 is most efficient (Table 5). The maximum flux J0,max of ditopic carrier 9 transporting CsClO4 is much lower than that of carrier 2, due to a lower diffusion coefficient Dm. This is attributed to the presence of the thiourea groups in the ditopic carrier. Small amounts of (thio)urea derivatives can serve as gelating agents (36) This demonstrates that extraction of KCl by anion carrier 5 individually is much less effective than the extraction of KCl by cation carrier 1. (37) The transport of KCl, CsCl, and CsClO4 facilitated by anion carrier 7 was too low to be determined (J0 < 0.5 × 10-8 mol m-2 s-1).

Figure 7. Transport of CsCl by ditopic carrier 9 (9) and monotopic carrier 2 ([) as a function of the source phase salt activity; [carrier]m ) 0.01 M.

for organic solvents, due to intermolecular hydrogen bonding of the (thio)urea moieties.38 This effect increases the viscosity of the membrane solvent and therefore retards the rate of diffusion. ∆Gex,NPOE(2‚CsClO4) is slightly higher than ∆Gex,NPOE(9‚CsClO4), indicating that the binding strength for Cs+ is not much affected by the thiourea moieties in carrier 9. The transport of CsCl by carriers 2 and 9 is totally different from the previous case (Figure 7). Although carrier 2 is the most efficient carrier for CsClO4, carrier 9 transports CsCl more efficiently. At [CsCl]s ) 0.1 M, the transport by 9 (J0 ) 23 × 10-8 mol m-2 s-1) is about 5 times higher than that by 2 (J0 ) 4.5 × 10-8 mol m-2 s-1), which clearly demonstrates that both binding sites are involved in the complexation of CsCl. The transport of CsCl by the monotopic 1,3-dioctyloxycalix[4]crown-6 carrier 2 is described by eq 1 (Table 5). When we assume that the Dm values of complexes 2‚CsCl and 2‚CsClO4 are about the same, the value for Kex of carrier 2 for CsCl can be determined from eq 1 (Kex ) 3.7 × 10-3 M-1) with a corresponding Gibbs free energy of ∆Gex,NPOE(CsCl) ) 13.9 kJ mol-1. Transport of CsCl by ditopic carrier 9 can no longer be described by the model for cation-facilitated transport but by the diffusion of a ditopic complex in which the Cs+ and Cl- are simultaneously bound as a ligand-separated ion pair. Therefore eq 11 holds for the flux as a function of the experimental parameters and Dm and K′ex.4b

[MLX]ms

+

Ms + Lms + Xs- / MLXms; K′ex )

J0 )

[

[M ]s[X-]s[L]ms (10)

DmK′exL0 as2 dm (1 + Kexas2)

+

]

(11)

The diffusion coefficient Dm and extraction constant K′ex of carrier 9‚CsCl were determined by fitting eq 11 to the data in Figure 7 (Table 5). The diffusion coefficient of carrier 9‚CsCl (Dm ) 4.2 × 10-12 m2 s-1) is low. Diffusion coefficients of macrocyclic complexes in SLMs are generally in the range of 10 × 10-12 m2 s-1.4 The relative order of the diffusion coefficients was confirmed with lag-time experiments; Dm(2‚ CsClO4) > Dm(9‚CsClO4) > Dm(9‚CsCl). The extraction constants for the transport of CsCl by 2 (Kex ) 3.7 × 10-3 M-1) and 9 (Kex′ ) 472 M-2) cannot be compared directly. However, when we calculate39 the percentage of complex 2‚CsCl and 9‚CsCl in the membrane phase after (38) Van Esch, J.; Kellogg, R. M.; Feringa, B. L. Tetrahedron Lett. 1997, 38, 281. (39) For the monotopic cation complex, the percentage of complex in the membrane phase is defined as % complex ) 100% × ([ML+]m/ [L]m,0) and follows from eq 2. For the ditopic complex, it is defined as % complex ) 100% × ([MLX]m/[L]m,0) and follows from eq 11.

10148 J. Am. Chem. Soc., Vol. 121, No. 43, 1999

Chrisstoffels et al.

Figure 8. Transport of CsCl by ditopic carrier 9 (9) and the mixture of carriers 2 and 7 ([) as a function of the source phase salt activity; [9]m ) 0.01 M and [2]m ) [7]m ) 0.01 M.

Figure 9. Transport of KCl by cation carrier 1 ([), the mixture of carriers 1 and 7 (b), and ditopic carrier 8 (9) as a function of the source phase salt activity; [8]m ) [1]m ) [7]m ) 0.01 M.

extraction from CsCl (as,CsCl ) 0.1 M) with 0.01 M carrier, 83% of the receptor 9 is present as complex, whereas only 6% of the monotopic carrier 2 is complexed. From the extraction constants Kex, K′ex (Table 5), and the ratio of the partition constants Kp(CsClO4)/Kp(CsCl) ) 8.5 × 105, the binding constant Ka,Cl for the complexation of Cl- by carrier 9 was calculated (eq 12); Ka,Cl ) 1 × 105 M-1 or ∆Ga(9‚Cl-) ) -28.5 kJ mol-1.

observed for the diffusion of amino acids as cationic species and as zwitterions.40 Facilitated Transport of KCl by a Cation Carrier, a Carrier Mixture, and a Bifunctional Carrier. Ultimately, we compared the transport of KCl for three different systems; (i) ditopic calix[4]crown-5 8, (ii) monotopic calix[4]crown-5 1, and (iii) the mixture of calix[4]crown-5 1 and calix[4]arene 7.37 The transport of KCl was measured as a function of the KCl activity (Figure 9). At low salt activity (as < 0.1 M), ditopic carrier 8 and the mixture of the monotopic cation carrier 1 and anion carrier 7 exhibit the highest flux. This is due to the enhanced extraction of KCl because of the additional binding site for chloride as anion carrier or in the bifunctional receptor. At high salt activity (as > 0.4 M), the transport rate of KCl by the carrier mixture of 1 and 7 as well as by ditopic carrier 8 reaches a maximum. The maximum flux J0,max of ditopic calix[4]crown-5 carrier 8 is much lower than that of the carrier mixture of calix[4]crown-5 1 and calix[4]arene 7. This difference is also observed for the transport of CsCl by the calix[4]crown6 carriers. Since the transport is diffusion-limited, the low maximum flux J0,max is attributed to the lower diffusion velocity of bifunctional carrier 8 compared to the mixture of anion carrier 7 and cation carrier 1. This hypothesis is supported by the diffusion coefficients Dm determined from the transport of KCl as a function of the membrane thickness. The diffusion coefficients decrease in the order Dm(1‚KCl) ) 10.4 × 10-12 m2 s-1 > Dm((1 + 7)‚KCl) ) 6.8 × 10-12 m2 s-1 > Dm(8‚ KCl) ) 3.9 × 10-12 m2 s-1. For diffusion-limited transport, J0,max at higher salt concentration is determined by the diffusion coefficient Dm. Therefore, when [KCl]s > 0.5 M, the transport rates decrease in the order J0(1) > J0(1 + 7) > J0(8). The monotopic calix[4]crown-5 carrier 1 becomes the most efficient carrier as it reaches the highest plateau J0,max, whereas under these conditions the lowest transport efficiency is obtained for ditopic carrier 8!

Ka,Cl )

Kp(CsClO4) Kp(CsCl)

×

K′ex(CsCl) Kex(CsClO4)

(12)

As Ka,Cl . 1 M-1, we can conclude that the complexation of Cl- in the bifunctional receptor clearly contributes to the extraction of CsCl by ditopic carrier 9. Ka,Cl is about 1 order of magnitude higher than those reported for the complexation of Cl- by the urea-based anion receptors in CDCl3 by Scheerder et al. (Ka,Cl ) 103 - 104 M-1).21d The enhanced binding affinity must be due to additional attractive electrostatic forces of Cs+ bound in the bifunctional receptor. We found that CsCl is transported selectively in the presence of a large excess of NaCl by ditopic carrier 9 ([CsCl]s ) 2.5 × 10-4 M and [NaCl]s ) 0.25 M), as about 87% of all CsCl was transported within 2 days. For monotopic carrier 2 the transport of CsCl was much lower, as only 3% of all Cs+ was transported after 2 days. Both for carrier 2 and for carrrier 9, Na+ could not be detected in the receiving phase even after 2 days. CsCl Transport Facilitated by a Ditopic Carrier and a Carrier Mixture. To evaluate the effect of covalent linkage of the two recognition sites on salt transport, we compared the transport of CsCl by ditopic bis(thioureido)calix[4]crown-6 9 and the mixture of bis(thioureido)calix[4]arene 7 and di-(1octyloxy)calix[4]crown-6 2. The transport of CsCl by the 1:1 carrier mixture of 2 and 7 (10 mM in NPOE) and by carrier 9 was studied as a function of the CsCl concentration (Figure 8). For both systems, a maximum flux J0,max is reached at higher salt concentration ([CsCl]s > 0.3 M). In contrast to what was expected on the basis of the size of the diffusing complexes, the carrier mixture of 2 and 7 transports CsCl more efficiently than ditopic carrier 9. There is a substantial difference in the maximum flux J0,max, namely, J0,max(9) ) 4.1 × 10-7 mol m-2 s-1 and J0,max(2 + 7) ) 6.3 × 10-7 mol m-2 s-1. The diffusion of the complex through the membrane phase is the rate-limiting step of transport of CsCl by both ditopic carrier 9 and the mixture of carriers 2 and 7.5 The diffusion coefficient of the carrier mixture is higher than of the ditopic carrier, which was confirmed by lag-time measurements. On the basis of the Stokes-Einstein, this result was unexpected. The lower diffusion velocity might be explained from the zwitterionic character of the complex. This has also been

Conclusions The cotransported anion largely influences the extraction efficiency in cation-facilitated transport, due to the unfavorable contribution of ∆Gex,NPOE(X-) to ∆Gex,NPOE(MX). Mixtures of cation carriers 1, 3, or 4 and anion carriers 5 or 6 cooperatively transport hydrophilic salts, such as KCl and KH2PO4. The transport is limited by the rate of diffusion, and the mean diffusion coefficient decreases with increasing number of carriers involved in transport. Addition of anion carrier 5 to cation carrier 1 does not always improve salt transport. At high salt concentration a single carrier system of carrier 1 is advantageous, whereas at low salt concentration the carrier (40) Cohn, E. J., Edstall, J. T., Eds. Proteins, Amino Acids and Peptides as Ions and Dipolar Ions; Hafner Publishing Company: New York, 1965.

Facilitated Transport of Hydrophilic Salts mixture of 1 and 5 is a more efficient system. KCl and CsCl were transported by ditopic receptors 8 and 9, respectively, by simultaneous complexation of both the cation and anion. Ditopic receptor 9 transports CsCl much more efficiently than cation carrier 2 or anion carrier 7. However, at high salt concentration, the transport of KCl by bifunctional carrier 8 is less effective than by cation carrier 1, due to the surprisingly low rate of diffusion of the bifunctional carrier complex. Experimental Section Melting points were determined with a Reichert melting point apparatus and are uncorrected. 1H NMR and 13C NMR spectra were recorded with a Bruker AC 250 spectrometer in CDCl3. The presence of solvent in the analytical samples was confirmed by 1H NMR spectroscopy. Fast atom bombardment (FAB) mass spectra were obtained with a Finnigan MAT 90 spectrometer. The spectra were obtained with use of m-nitrobenzyl alcohol as a matrix. CH2Cl2 was distilled from CaH2 and stored over molecular sieves (4 Å) prior to use. CH3CN and DMSO were dried over molecular sieves (4 Å) prior to use. Petroleum ether refers to the fraction with bp 4060 °C. Other chemicals were of reagent grade and were used without purification. Column chromatography was performed with silica gel (Merck; 0.015-0.040 mm) unless stated otherwise. All reactions were carried out under an argon atmosphere. Carriers 1,22 2,23 3,41 and 1042 were synthesized according to literature procedures. The synthesis of carriers 5 and 6 is described elsewhere.19 2-[[8-(2-Nitrophenoxy)-1-octyloxy]methyl]-15-crown-5 (4). NaH (60%) as suspension in mineral oil (76 mg, 1.9 mmol) was washed twice with petroleum ether. Then THF (50 mL) was added followed by 2-hydroxymethyl-15-crown-5 (400 mg, 1.6 mmol). The mixture was stirred for 1 h. Subsequently, 8(-bromooctyl)-2-nitrophenyl ether (690 mg, 2.1 mmol) was added and the mixture was refluxed for 24 h. Water was added slowly, and the aqueous solution was extracted with CH2Cl2 (2 × 100 mL). The organic layer was washed with water (2 × 100 mL) and dried over MgSO4. The crude residue was purified by column chromatography (SiO2, CH2Cl2/MeOH ) 95:5) to obtain 4 as a yellow oil. Yield 46%; ND20 1.5425; 1H NMR δ 7.76 (dd, 1 H, Jo ) 8.1 Hz, Jm ) 1.7 Hz, ArH), 7.5-7.35 (m, 1 H, ArH), 7.0-6.85 (m, 2H, ArH), 4.04 (t, 2H, J ) 6.4 Hz, ArOCH2), 3.8-3.4 (m, 19H, OCH2CH2), 3.43.25 (m, 4H, OCHCH2O and OCH2CH2CH2), 1.85-1.65 (m, 2H, ArOCH2CH2), 1.6-1.4 (m, 4H, CH2OCH2CH2 and ArOCH2CH2CH2), 1.35-1.1 (s, 6H, CH2); 13C NMR δ 152.5 (s, ArCO), 139.9 (s, ArCNO2), 134.0-114.5 (d, ArCH), 78.6 (d, OCH), 71.6-69.5 (t, CH2O), 29.6-25.8 (t, CH2CH2CH2); MS-FAB m/z 523.0 [(M + Na)+, calcd 523.0]. 25,27-Dipropoxy-26,28-bis[(3-(N′-(2-ethylhexyl)thioureido)propyl)oxy] calix[4]arene (7), 1,3-Alternate. A solution of calix[4]arene 14 (0.50 g, 0.71 mmol) and 2-ethylhexylamine (0.58 mL, 3.5 mmol) in dry CH2Cl2 (100 mL) was stirred in a closed tube at room temperature for 10 h. Then CH2Cl2 was removed under reduced pressure. The solid was purified by column chromatography (CH2Cl2) and preparative TLC (hexane/EtOAc ) 4:1) to afford 7 as a white solid. Yield 59%; mp 118-120 °C; 1H NMR(400 MHz) δ 7.05 (d, 4 H, J ) 7.2 Hz, ArHm), 7.01 (d, 4 H, J ) 7.2 Hz, ArH-m), 6.87 (t, 2 H, J ) 7.4 Hz, ArHp), 6.80 (t, 2 H, J ) 7.6 Hz, ArH-p), 6.07 (bs, 4 H, NH), 3.81 (s, 8 H, ArCH2Ar), 3.47 (bs, 8 H, CH2CH2N and NCH2CH), 3.4-3.3 (m, 8 H, J ) 7.6 Hz, OCH2C2H5 and OCH2(CH2)2N), 1.7-1.55 (m, 2 H, NCH2CH), 1.55-1.45 (m, 4 H, CH2CH2N), 1.45-1.2 (m, 16 H, CH3(CH2)3CH(CH2CH3)), 1.15-1.0 (m, 4 H, CH2CH3), 0.95-0.8 (m, 12 H, CH3(CH2)3CH(CH2CH3)), 0.65 (t, 6 H, J ) 7.6 Hz, CH3); 13C NMR(400 MHz) δ 181.7 (s, CdS), 157.1, 156.2 (s, ArC-O), 134.3, 133.2 (s, ArC-o), 129.2, 128.9 (d, ArC-m), 122.2, 121.4 (d, ArC-p), 71.6, 67.0 (t, OCH2C2H4N and OCH2C2H5), 47.7, 40.6 (t, CH2N), 38.9 (d, CHCH2N), 38.0 (t, ArCH2Ar), 30.8, 29.4, 28.6, 24.0, 22.8, 21.9 (t, CH3(CH2)3CH(CH2CH3) and CH2CH2N and CH2CH3), 13.8, 10.6, 9.6 (q, (41) Arnaud-Neu, F.; Collins, E. M.; Deasy, M.; Ferguson, G.; Harris, S. J.; Kaitner, B.; Lough, A. J.; McKervey, M. A.; Marques, E.; Ruhl, B. L.; Swing-Weil, M. J.; Seward, E. M. J. Am. Chem. Soc. 1989, 111, 8681. (42) Gutsche, C. D.; Lin, L.-G. Tetrahedron 1986, 51, 742.

J. Am. Chem. Soc., Vol. 121, No. 43, 1999 10149 CH3); IR (KBr) 3266 cm-1 (NH); MS-FAB m/z 963.5 [(M-H)-, calcd 963.6]. Anal. calcd for C58H84N4O4S2: C, 72.16; H, 8.77; N, 5.80. Found: C, 72.53; H, 8.71; N, 5.70. General Procedure for the Synthesis of 25,27-Bis[(3-(N′-(2ethylhexyl) thioureido)propyl)oxy]calix[4]arene-crown-n (n ) 5, 6), 1,3-Alternate. A solution of calix[4]arene-crown-n (n ) 5, 6) 20 or 19 (0.64 mmol) and 2-ethylhexylamine (0.25 g, 1.92 mmol) in dry CH2Cl2 (50 mL) was stirred in a closed tube at room temperature for 10 h. Then CH2Cl2 was removed under reduced pressure. The pure compound were obtained after preparative TLC as a viscous oil (CH2Cl2/EtOAc ) 19:1 and subsequently increasing the polarity with EtOAc). 25,27-Bis[(3-(N′-(2-ethylhexyl)thioureido)propyl)oxy]calix[4]arenecrown-5 (8). Yield 77%; 1H NMR δ 7.09 (d, 4 H, J ) 7.5 Hz, ArHm), 7.06 (d, 4 H, J ) 7.5 Hz, ArH-m), 7.0-6.8 (m, 4 H, ArH-p), 6.12 (bs, 4 H, NH), 3.85 (s, 8 H, ArCH2Ar), 3.7-3.4 (m, 20 H, ArOCH2CH2OCH2CH2 and OCH2CH2CH2N), 3.2-3.0 (m, 8 H, ArOCH2CH2O and NCH2CH), 1.65-1.55 (m, 2 H, NCH2CH), 1.5-1.2 (m, 20 H, CH3(CH2)3CH(CH2CH3) and OCH2CH2CH2N), 1.0-0.8 (m, 12 H, CH3); 13C NMR δ 182.4 (s, CS), 156.9 (s, ArC-O), 134.8, 133.8 (s, ArC-o), 129.5 (d, ArC-m), 123.2, 122.6 (d, ArC-p), 73.3, 71.1, 69.7, 68.1, 67.6 (t, OCH2CH2O and ArOCH2), 48.3, 41.0 (t, CH2N), 39.5 (d, CH3(CH2)3CH(C2H5)), 38.5 (t, ArCH2Ar), 31.5, 30.0, 29.2, 24.7, 23.3 (t, CH3(CH2)3CH(CH2CH3)CH2N and OCH2CH2CH2N), 14.3, 11.2 (q, CH3); MS-FAB m/z 1037.3 [(M - H)-, calcd 1037.6]. 25,27-Bis[(3-(N′-(2-ethylhexyl)thioureido)propyl)oxy]calix[4]arenecrown-6 (9). Yield 95%; 1H NMR δ 7.1-7.0 (m, 8 H, ArH-m), 6.956.85 (m, 4 H, ArH-p), 3.84 (s, 8 H, ArCH2Ar), 3.69 (s, 4 H, ArO(CH2CH2O)2CH2), 3.65-3.45 (m, 20 H, ArOCH2CH2O(CH2)2O and OCH2CH2CH2N), 3.2-3.0 (m, 8 H, ArOCH2CH2OC2H4 and NCH2CH), 1.62 (bs, 2 H, NCH2CH), 1.5-1.2 (m, 20 H, CH3(CH2)3CH(CH2CH3) and OCH2CH2CH2N), 1.0-0.8 (m, 12 H, CH3); 13C NMR δ 182.4 (s, CS), 157.2, 157.0 (s, ArC-O), 134.5, 133.9 (s, ArC-o), 129.8 (d, ArC-m), 123.0, 122.6 (d, ArC-p), 71.3, 71.2, 71.0, 69.5, 69.2, 67.6 (t, OCH2CH2O and ArOCH2), 48.3, 41.1 (t, CH2N), 39.5 (d, CHCH2N), 38.5 (t, ArCH2Ar), 31.4, 30.6, 29.2, 24.7, 23.3 (t, CH3(CH2)3CH(CH2CH3) and OCH2CH2CH2N), 14.3, 11.1 (q, CH3); MS-FAB m/z 1081.1 [(M - H)-, calcd 1081.6]. 25,27-Bis[(3-phthalimidopropyl)oxy]calix[4]arene (11). A mixture of 25,26,27,28-tetrahydroxycalix[4]arene 10 (1.00 g, 2.35 mmol), N-(3bromopropyl)phthalimide (1.32 g, 4.94 mmol), K2CO3 (0.39 g, 2.82 mmol), and a catalytic amount of KI in dry CH3CN (30 mL) was refluxed for 60 h. Then the solvent was removed under reduced pressure. The residue was dissolved in CH2Cl2 (100 mL) and washed with 1 N NH4Cl (2 × 25 mL). The organic phase was separated, dried with MgSO4, and evaporated to dryness to afford a white solid that was triturated with CH3CN. Yield 80%; mp 302-304 °C; 1H NMR δ 7.95 (s, 2 H, OH), 7.85-7.70 (m, 8 H, Ph-H pht), 7.09 (d, 4 H, J ) 9.5 Hz, ArH-m), 6.88 (d, 4 H, J ) 10.7 Hz, ArH-m), 6.69 (t, 2 H, J ) 9.5 Hz, ArH-p), 6.63 (t, 2 H, J ) 10.7 Hz, ArH-p), 4.35 (d, 4 H, J ) 13.0 Hz, ArCHaxAr), 4.18 (t, 8 H, J ) 5.9 Hz, OCH2CH2CH2N), 3.45 (d, 4 H, J ) 11.9 Hz, ArCHeqAr), 2.51 (q, 4 H, J ) 5.9 Hz, OCH2CH2CH2N); 13C NMR δ 168.2 (s, CdO), 153.3, 151.9 (2s, ArC-O), 133.7 (d, PhCH, pht), 133.2, 132.1 (s, ArC-o), 128.9, 128.4 (d, ArC-m), 128.0 (s, PhC, pht), 125.3, 123.1 (d, PhCH, pht), 119.0 (d, ArC-p), 74.6 (t, OCH2), 35.7 (t, NCH2), 31.4 (t, ArCH2Ar), 29.4 (t, OCH2CH2CH2N); MS-FAB m/z 798.3 (M+, calcd 798.9). Anal. calcd for C50H42N2O8‚ 2CH3CN: C, 73.62; H, 5.49; N, 6.36. Found: C, 73.77; H, 5.54; N, 6.28. 25,27-Dipropoxy-26,28-bis[(3-phthalimidopropyl)oxy]calix[4]arene (12), 1,3-Alternate. A solution of calix[4]arene 11 (1.0 g, 1.25 mmol), Cs2CO3 (1.6 g, 4.9 mmol), and PrI (1.3 g, 7.5 mmol) in dry MeCN (100 mL) was refluxed for 3 days. Then the solvent was removed under reduced pressure. Subsequently, the residue was dissolved in CH2Cl2 (70 mL) and washed with 1 N NH4Cl (3 × 50 mL) and water (2 × 50 mL). The organic phase was separated, dried with MgSO4, and evaporated to afford a solid, which was crystallized from MeOH to give 27 as a pure white powder. Yield 52%; mp 208-211 °C; 1H NMR δ 7.9-7.6 (m, 8 H, PhH pht), 7.1-6.9 (m, 8 H, ArH-m), 6.81 (t, 2 H, J ) 7.3 Hz, ArH-p), 6.72 (t, 2 H, J ) 7.5 Hz, ArH-p), 3.68 (s, 8 H, ArCH2Ar), 3.62 (t, 4 H, J ) 3.2 Hz, OCH2(CH2)2N), 3.51, 3.43 (2 × t, 8 H, J ) 3.0 Hz and J ) 3.0 Hz, CH2N and OCH2C2H5), 1.9-

10150 J. Am. Chem. Soc., Vol. 121, No. 43, 1999 1.6 (m, 4 H, CH2CH2N), 1.5-1.4 (m, 4 H, CH2CH3), 0.78 (t, 6 H, J ) 7.5 Hz, OCH2CH2CH3); 13C NMR δ 168.3 (s, CdO), 156.7, 156.3 (s, ArC-O), 133.9, 133.8 (s, ArC-o), 133.8 (d, PhCH, pht), 132.2 (s, PhC, pht), 129.8, 129.6 (d, ArC-m), 123.3, 123.2 (d, ArC-p), 122.3, 122.0 (d, PhCH, pht), 72.8, 68.7 (t, OCH2CH2CH3 and OCH2CH2CH2N), 37.3 (t, ArCH2Ar), 35.3 (t, CH2N), 29.1 (t, CH2CH2N), 23.1 (t, CH2CH3), 10.3 (q, OCH2CH2CH3); IR (KBr) 1714 cm-1 (CdO); MS-FAB m/z 905.5 [(M + Na)+, calcd 905.4]. Anal. calcd for C56H54N2O8‚0.5H2O: C, 75.40; H, 6.21; N, 3.14. Found: C, 75.17; H, 6.05; N, 3.16. 25,27-Dipropoxy-26,28-bis[(3-aminopropyl)oxy]calix[4]arene (13), 1,3-Alternate. A solution of calix[4]arene 27 (0.20 g, 0.23 mmol) and NH2NH2‚H2O (0.22 g, 4.5 mmol) in ethanol (30 mL) was stirred in a closed tube at 110-120 °C for 8 h. Then the solvent was removed under reduced pressure. The residue was dissolved in CH2Cl2 (30 mL) and washed with a solution of NH4OH (pH ≈ 9) (3 × 15 mL). The organic phase was separated, dried with MgSO4, and evaporated to afford 13 as a pure solid. Yield 96%; mp 195-198 °C; 1H NMR δ 7.0-6.9 (m, 8 H, ArH-m), 6.8-6.6 (m, 4 H, ArH-p), 3.61 (s, 8 H, ArCH2Ar), 3.56, 3.39 (2 × t, 8 H, J ) 6.6 Hz and J ) 7.5 Hz, OCH2CH2CH2N and OCH2CH2CH3), 2.62 (t, 4 H, J ) 6.8 Hz, CH2N), 1.71.55 (m, 4 H, CH2CH2N), 1.45-1.3 (m, 4 H, CH2CH3), 0.76 (t, 6 H, J ) 7.5 Hz, CH3); 13C NMR δ 156.7 (s, ArC-O), 134.0, 133.7 (s, ArC-o), 129.9, 129.7 (d, ArC-m), 121.9, 121.7 (d, ArC-p), 72.9, 70.2 (t, OCH2), 39.9 (t, NCH2), 37.1 (t, ArCH2Ar), 34.1 (t, CH2CH2N), 23.0 (t, CH2CH3), 10.3 (q, CH3); IR (KBr) 3369 cm-1 (NH2); MS-FAB m/z 623.3 [(M + H)+, calcd 623.4]. Anal. calcd for C40H50N2O4: C, 77.14; H, 8.09; N, 4.50. Found: C, 77.68; H, 8.14; N, 4.48. 25,27-Dipropoxy-26,28-bis[(3-isothiocyanatopropyl)oxy]calix[4]arene (14), 1,3-Alternate. A solution of calix[4]arene 13 (0.50 g, 0.80 mmol), thiophosgene (0.50 g, 3.2 mmol), and NEt3 (0.80 g, 8.0 mmol) in dry toluene (160 mL) was heated to 60 °C for 6 h. The solvent was removed under reduced pressure, after which the crude product was dissolved in CH2Cl2 (20 mL) and washed with water (3 × 10 mL). The organic phase was dried with MgSO4 and evaporated under reduced pressure. The residue was purified by column chromatography (hexane/ EtOAc ) 1:1) and crystallization from MeOH. Yield 62%; mp 177179 °C; 1H NMR(400 MHz) δ 7.1-7.0 (m, 8 H, ArH-m), 6.88 (t, 2 H, J ) 7.6 Hz, ArH-p), 6.82 (t, 2 H, J ) 7.4 Hz, ArH-p), 3.81, 3.79 (2 × d, 8 H, J ) 6.8 Hz, J ) 10.4 Hz, ArCH2Ar), 3.64, 3.36 (2 × t, 8 H, J ) 6.4 Hz, J ) 7.8 Hz, OCH2C2H5 and OCH2(CH2)2N), 3.11 (t, 4 H, J ) 6.6 Hz, CH2N), 1.8-1.6 (m, 4 H, CH2CH2N), 1.2-1.0 (m, 4 H, CH2CH3), 0.68 (t, 6 H, J ) 7.2 Hz, CH3); 13C NMR(400 MHz) δ 157.0, 156.2 (s, ArC-O), 134.2, 133.5 (s, ArC-o), 129.5, 129.1 (d, ArC-m), 122.6, 122.0 (d, ArC-p), 71.8, 66.2 (t, OCH2(CH2)2N and OCH2C2H5), 41.8 (t, CH2N), 38.1 (t, ArCH2Ar), 30.4 (t, CH2CH2N), 22.3 (t, CH2CH3), 9.9 (q, CH3); IR (KBr) 2094 cm-1 (NdCdS); MS-FAB m/z 707.7 [(M + H)+, calcd 707.3]. Anal. calcd for C42H46N2O4S2: C, 71.36; H, 6.56; N, 3.96. Found: C, 71.04; H, 6.51; N, 3.92. General Procedure for the Synthesis of 25,27-Bis[(3-phthalimidopropyl)oxy] calix[4]arene-crown-n (n ) 5, 6), 1,3-Alternate. A solution of calix[4]arene 11 (2.00 g, 2.5 mmol), Cs2CO3 (4.00 g, 12.3 mmol), and tetra- or pentaethylene glycol di-p-toluenesulfonate (2.58 mmol) in dry MeCN (500 mL) was refluxed for 5 days. Subsequently, the solvent was removed under reduced pressure. The residue was dissolved in CH2Cl2 (40 mL) and washed with 1 N NH4Cl (3 × 20 mL). The organic phase was separated, dried with MgSO4, and evaporated to afford a brown solid, which was purified by column chromatography (CH2Cl2/MeOH ) 95:5). 25,27-Bis[(3-phthalimidopropyl)oxy]calix[4]arene-crown-5 (15). Yield 40%; mp 106-108 °C; 1H NMR δ 7.9-7.7 (2 × m, 2 × 4 H, PhH pht), 7.10 (d, 4 H, J ) 8.7 Hz, ArH-m), 7.02 (d, 4 H, J ) 8.0 Hz, ArH-m), 6.87 (t, 4 H, J ) 8.0 Hz, ArH-p), 3.82 (s, 8 H, ArCH2Ar), 3.60 (s, 8 H, ArO(CH2)2OCH2CH2), 3.55-3.35 (m, 12 H, ArOCH2CH2O and OCH2CH2CH2N), 3.15 (t, 4 H, J ) 7.0 Hz, ArOCH2CH2O), 1.6-1.4 (m, 4 H, CH2CH2N); 13C NMR δ 168.2 (s, CdO), 156.5, 156.1 (s, ArC-O), 134.1, 134.0 (s, ArC-o), 133.7 (d, PhCH, pht), 132.1 (s, PhC, pht), 129.2, 129.1 (d, ArC-m), 123.1, 123.0 (d, ArC-p), 122.6 (d, PhCH, pht), 72.6, 70.6, 69.9, 68.3, 67.8 (t, OCH2CH2O and ArOCH2), 38.1 (t, ArCH2Ar), 35.0 (t, CH2N), 28.5 (t, CH2CH2N); MS-FAB m/z 979.6 [(M + Na)+, calcd 979.4]. Anal. calcd for C58H56N2O11: C, 72.79; H, 5.90; N, 2.93. Found: C, 73.04; H, 5.68; N, 3.03.

Chrisstoffels et al. 25,27-Bis[(3-phthalimidopropyl)oxy]calix[4]arene-crown-6 (16). Yield 78%; mp 180-181 °C; 1H NMR δ 7.85-7.70 (m, 8 H, PhH pht), 7.07 (d, 4 H, J ) 8.0 Hz, ArH-m), 7.00 (d, 4 H, J ) 8.0 Hz, ArH-m), 6.80 (t, 4 H, J ) 8.0 Hz, ArH-p), 3.78 (s, 8 H, ArCH2Ar), 3.68 (s, 4 H, ArO(CH2CH2O)2CH2), 3.65-3.40 (m, 20 H, OCH2CH2OCH2CH2OCH2 and CH2CH2CH2N), 3.16 (t, 4 H, J ) 7.1 Hz, ArOCH2CH2O), 1.6-1.4 (m, 4 H, CH2CH2N); 13C NMR δ 168.2 (s, CdO), 156.5 (s, ArC-O), 134.0, 133.8 (s, ArC-o), 133.7 (d, PhCH, pht), 132.1 (s, PhC, pht), 129.6, 129.5 (d, ArC-m), 123.1, 122.9 (d, ArC-p), 122.5 (d, PhCH, pht), 71.1, 70.9, 69.7, 67.9 (t, OCH2CH2O and ArOCH2), 38.0 (t, ArCH2Ar), 35.0 (t, CH2N), 28.5 (t, CH2CH2N); MS-FAB m/z 1023.9 [(M + Na)+, calcd 1024.1]. Anal. calcd for C60H60N2O12‚2H2O: C, 69.48; H, 6.22; N, 2.70. Found: C, 69.38; H, 5.79; N, 2.67. General Procedure for the Synthesis of 25,27-Bis[(3-aminopropyl)oxy]calix[4]arene-crown-n (n ) 5, 6), 1,3-alternate. To a solution of calix[4]crown-n (n ) 5, 6) 16 or 15 (0.62 mmol) in ethanol (30 mL) was added NH2NH2‚H2O (0.63 g, 12.6 mmol). The reaction mixture was stirred in a closed tube at 110 °C for 10 h. Then the solvent was evaporated, and the remaining solid was dissolved in CH2Cl2 (25 mL) and washed with a 1 mM solution of NaOH (3 × 15 mL) and water (2 × 15 mL). The organic phase was dried with MgSO4. Removal of the solvent under reduced pressure gave the desired bis[(3-aminopropyl)oxy]calix[4]crown-n (n ) 5, 6) derivatives 18 and 17. 25,27-Bis[(3-aminopropyl)oxy]calix[4]arene-crown-5 (17). Yield 87%; mp 146-148 °C; 1H NMR (300 MHz, CDCl3) δ 7.12 (d, 4 H, J ) 7.4 Hz, ArH-m), 7.05 (d, 4 H, J ) 7.5 Hz, ArH-m), 6.88 (t, 4 H, J ) 7.3 Hz, ArH-p), 3.84 (s, 8 H, ArCH2Ar), 3.7-3.6 (m, 8 H, OCH2CH2O), 3.57 (t, 4 H, J ) 6.25 Hz, ArOCH2CH2O), 3.44 (t, 4 H, J ) 6.80 Hz, OCH2(CH2)2N), 3.10 (t, 4 H, J ) 6.8 Hz, ArOCH2CH2O), 2.48 (t, 4 H, J ) 6.6 Hz, CH2N), 1.57 (bs, 4 H, NH2), 1.55-1.4 (m, 4 H, CH2CH2N); 13C NMR δ 161.0 (s, ArC-O), 134.5, 134.3 (s, ArCo), 129.7 (d, ArC-m), 122.8 (d, ArC-p), 73.1, 71.0, 69.9, 69.6, 68.2 (t, OCH2), 39.6 (t, ArCH2Ar), 38.5 (t, CH2CH2N), 29.9 (t, CH2CH2N); IR (KBr) 3404 cm-1 (NH2); MS-DCI m/z, 697.5 [(M + H)+, calcd 697.4]. 25,27-Bis[(3-aminopropyl)oxy]calix[4]arene-crown-6 (18). Yield 88%; mp 159-160 °C; 1H NMR (300 MHz, CDCl3) δ 7.07 (d, 4 H, J ) 6.1 Hz, ArH-m), 7.05 (d, 4 H, J ) 6.1 Hz, ArH-m), 6.9-6.8 (m, 4 H, ArH-p), 3.80 (s, 8 H, ArCH2Ar), 3.7-3.5 (m, 20 H, OCH2 and ArOCH2(CH2)N), 3.29 (t, 4 H, J ) 6.2 Hz, ArOCH2CH2O), 2.90 (bs, 4 H, CH2NH2), 2.16 (bs, 4 H, NH2), 1.55-1.4 (m, 4 H, CH2CH2N); 13C NMR δ 156.3, 155.3 (s, ArC-O), 134.5, 133.3 (s, ArC-o), 129.9, 129.7 (d, ArC-m), 123.4, 122.7 (d, ArC-p), 70.7, 70.6, 70.5, 69.3, 69.0, 68.9 (t, OCH2), 38.3 (t, ArCH2Ar), 37.5 (t, CH2N), 29.2 (t, CH2CH2N); IR (KBr) 3380 cm-1 (NH2); MS-DCI m/z, 741.4 [(M + H)+, calcd 741.4]. General Procedure for the Synthesis of 25,27-Bis[(3-isothiocyanatopropyl)oxy] calix[4]arene-crown-n (n ) 5, 6), 1,3-Alternate. Thiophosgene (0.33 g, 2.9 mmol) and NEt3 (0.73 g, 7.2 mmol) were added to a solution of calix[4]arene-crown-n (n ) 5-6) 18 or 17 (0.72 mmol) in dry toluene (100 mL). The solution was stirred and heated at 60 °C for 6 h, after which the solvent was removed under reduced pressure. The crude product was dissolved in CH2Cl2 (20 mL) and washed with water (3 × 10 mL). The organic phase was dried with MgSO4 and evaporated under reduced pressure. The residual solid was purified by column chromatography (CH2Cl2/EtOAc ) 4:1). 25,27-Bis[(3-isothiocyanatopropyl)oxy]calix[4]arene-crown-5 (19). Yield 67%; mp 184-186 °C; 1H NMR δ 7.12 (d, 4 H, J ) 7.4 Hz, ArH-m), 7.07 (d, 4 H, J ) 7.4 Hz, ArH-m), 6.95-6.85 (m, 4 H, ArHp), 3.87 (s, 8 H, ArCH2Ar), 3.7-3.5 (m, 12 H, ArOCH2CH2OCH2CH2O), 3.46 (t, 4 H, J ) 6.7 Hz, OCH2CH2CH2N), 3.03 (t, 4 H, J ) 6.5 Hz, OCH2CH2CH2N), 3.02 (t, 4 H, ArOCH2CH2O), 1.7-1.5 (m, 4 H, OCH2CH2CH2N); 13C NMR δ 157.0 (s, ArC-O), 134.5, 133.9 (s, ArC-o), 129.6, 129.3 (d, ArC-m), 125.9 (s, NCS), 123.4, 122.9 (d, Ar-p), 73.3, 71.1, 70.2, 69.8, 68.1, 66.4 (t, OCH2CH2O and ArOCH2), 42.0 (t, CH2NCS), 38.4 (t, ArCH2Ar), 30.6 (t, CH2CH2NCS); MS-DCI m/z 780.0 [M+, calcd 780.5]. 25,27-Bis[(3-isothiocyanatopropyl)oxy]calix[4]arene-crown-6 (20). Yield 63%; mp 179-180 °C; 1H NMR δ 7.11 (d, 4 H, J ) 7.6 Hz, ArH-m), 7.07 (d, 4 H, J ) 7.7 Hz, ArH-m), 6.95-6.85 (m, 4 H, ArHp), 3.85 (s, 8 H, ArCH2Ar), 3.70 (s, 4 H, ArO(CH2CH2O)2CH2), 3.7-

Facilitated Transport of Hydrophilic Salts 3.4 (m, 16 H, ArOCH2CH2OCH2CH2O and OCH2(CH2)2N), 3.14 (t, 4 H, J ) 6.7 Hz, CH2N), 3.08 (t, 4 H, J ) 6.8 Hz, ArOCH2CH2O), 1.61.4 (m, 4 H, CH2CH2N); 13C NMR (CDCl3) δ 157.0, 156.7 (s, ArCO), 134.3, 134.0 (s, ArC-o), 129.9, 129.6 (d, ArC-m), 125.9 (s, NCS), 123.3, 122.8 (d, ArC-p), 71.4, 71.3, 71.1, 70.2, 69.5, 69.1, 66.5 (t, OCH2CH2O and ArOCH2), 42.1 (t, CH2NCS), 38.4 (t, ArCH2Ar), 30.6 (t, CH2CH2NCS); MS-DCI m/z 824.6 [M+, calcd 824.4]. Transport Measurements. The polymeric film Accurel 1E-PP was obtained from Enka Membrana (thickness dm ) 100 µm, porosity τ ) 64%). o-Nitrophenyl n-octyl ether (NPOE) was purchased from Fluka and was used without further purification. All salts were of analytical grade and were obtained from Across. The transport experiments were performed at 298 K in an apparatus of which the details are described elsewhere.43 The carrier was dissolved in o-nitrophenyl n-octyl ether (NPOE) and immobilized in the solid support according to a standard procedure previously described by our group.43 The aqueous solutions were prepared with doubly distilled and deionized water. The transport of single salts was monitored by a measurement of the conductivity with time (Radiometer CDM 83). The concentration was calculated using a constant that correlates the conductivity to the concentration. The activity was determined by calculation of the activity coefficient using the Debye-Hu¨ckel equation.44 The transport rates of KH2PO4 (43) Stolwijk, T. B.; Sudho¨lter, E. J. R.; Reinhoudt, D. N. J. Am. Chem. Soc. 1987, 109, 7042. (44) Meier, P. C. Anal. Chim. Acta 1982, 136, 363.

J. Am. Chem. Soc., Vol. 121, No. 43, 1999 10151 and NaH2PO4 were determined by phosphate analysis of the receiving phase after 14 h of transport. From the receiving phase, several aliquots of 100 µL were taken. To each sample was added 1 mL of commercial phosphorus reagent (Sigma chemicals). The reaction of the inorganic phosphorus with ammonium molybdate in the presence of sulfuric acid produces an unreduced phosphomolybdate complex, of which the absorbance at 320 nm is proportional to the phosphorus concentration. In the case of competitive transport, the transport was monitored by atomic absorption measurements of samples from the receiving phase. The lag-time experiments and the transport at different membrane thickness have been carried out according to literature procedures.5 Caution: Care should be taken when handling uranyl-containing compounds because of their toxicity and radioactiVity.45

Supporting Information Available: Equations to calculate the Extraction efficiency of salts by a mixture of anion and cation carrier via a 1:1 complex or via a 1:1 cation complex and a 2:1 anion complex; transport model for facilitated transport of salt by a mixture of anion and cation receptor; two figures with calculated extraction efficiencies (PDF). This material is available free of charge via the Internet at http://pubs.acs.org. JA991588G (45) Sax, N. I., Ed. Dangerous Properties of Industrial Materials, 5th ed.; van Nostrand Reinhold Company: New York, 1979; p 1078.